Because we observed that some patients treated with immunotoxins developed anti-tumor immunity, we have developed a syngeneic mouse tumor model to study interactions of the immune system with immunotoxin therapy. We have developed syngeneic mouse models to evaluate the combination of LMB-100 and check point inhibitors. We find that the direct injection of LMB-100 into tumors synergizes with anti-CTLA-4 given I.P. to produce complete tumor regressions and the development of anti-tumor immunity. These studies were done in a mouse breast cancer model and are being extended to other cancer types to determine how general the effect is. We are also evaluating other check point inhibitors. Based on these studies a clinical trial combining LMB-100 with a check point inhibitor is being planned to open at NCI this year in mesothelioma and lung cancer. To develop a new treatment for myeloma we have made new immunotoxins targeting BCMA that is expressed on almost all myelomas. To evaluate these immunotoxins in a relevant animal model, we produced myeloma cells expressing luciferase and grow them in mouse bone marrow. We find the anti-BCMA immunotoxins are very active in this model and are looking for a company to help develop these agents for clinical trials.